Human pancreatic adenocarcinomas have the lowest 5-year survival rate of all common cancers. The five-year survival rate of persons with adenocarcinoma of the pancreas is 1%. The median survival is 4.1 months. Current cancer chemotherapy and surgery prolong survival by a few months but the above survival rates are for persons treated with surgery and/or currently available cancer chemotherapeutic agents.
A family of peptides referred to as atrial natriuretic peptides (ANPs) are synthesized within the heart and stored in the atrial myocyte as prohormones for rapid release in response to stimuli. The atrial natriuretic peptide (ANP) gene synthesizes a 126 amino acid (a.a.) prohormone which contains four peptide hormones consisting of a.a. 1-30 (i.e., long acting natriuretic peptide, LANP) a.a. 31-67 (vessel dilator), a.a. 79-98 (kaliuretic peptide) and atrial natriuretic peptide (ANP, a.a, 99-126 of this prohormone). Known biologic properties of these four peptide hormones include blood pressure lowering, diuresis, enhanced sodium and/or potassium excretion when infused into healthy animals and humans. One of these peptide hormones, i.e., ANP has been investigated for growth regulatory properties. In blood vessels, ANP inhibits smooth muscle cell proliferation (hyperplasia) as well as smooth muscle cell growth (hypertrophy). ANP has growth-regulatory properties in a variety of other tissues including brain, bone, myocytes, red blood cell precursors, and endothelial cells. In the kidney, ANP causes antimitogenic and antiproliferative effects in glomerular mesangial cells via inhibiting DNA synthesis. [Cyclic GMP] mediates most of the effects of these four peptide hormones. Thus, cyclic GMP causes vasodilation by itself and mediates the blood pressure lowering effects of these hormones. Vessel dilator and LANP as well as ANP enhance membrane-bound guanylate cyclase to increase cyclic GMP in vasculature. Cyclic GMP [i.e., 8-bromoguanosine 3′,5′-cyclic monophosphate] decreases the number of human breast and prostate adenocarcinomas, as well as small-cell and squamous cell lung carcinoma cells in culture by 30% (1 μM), 84% (1 mM), 31% (1 μM) and 30% (1 μM).